Characterization of an HNA aptamer suggests a non-canonical G-quadruplex motif.

Nucleic acids not only form the basis of heredity, but are increasingly a source of novel nano-structures, -devices and drugs. This has spurred the development of chemically modified alternatives (xeno nucleic acids (XNAs)) comprising chemical configurations not found in nature to extend their chemical and functional scope. XNAs can be evolved into ligands (XNA aptamers) that bind their targets with high affinity and specificity. However, detailed investigations into structural and functional aspects of XNA aptamers have been limited. Here we describe a detailed structure-function analysis of LYS-S8-19, a 1',5'-anhydrohexitol nucleic acid (HNA) aptamer to hen egg-white lysozyme (HEL). Mapping of the aptamer interaction interface with its cognate HEL target antigen revealed interaction epitopes, affinities, kinetics and hot-spots of binding energy similar to protein ligands such as anti-HEL-nanobodies. Truncation analysis and molecular dynamics (MD) simulations suggest that the HNA aptamer core motif folds into a novel and not previously observed HNA tertiary structure, comprising non-canonical hT-hA-hT/hT-hT-hT triplet and hG4-quadruplex structures, consistent with its recognition by two different G4-specific antibodies.

Diagnostic Schemas: Form and Function.

Diagnostic schemas are frameworks that depict organized clinical knowledge and serve as a bridge between problem representation and differential diagnosis generation. Schema-based problem solving is increasingly used among clinician educators and is widely featured in digital media. We examine the origins of schemas and their theoretical background, review existing literature on their applications in medicine, and explore their utility for learners and teachers.

Mission Critical: Reimagining Promotion for Clinician-Educators.

Academic clinician-educators who teach health professions trainees and lead educational programs have been penalized by the mismatch between their daily contributions to the academic mission and traditional promotion criteria focused on peer-reviewed publications and external reputation. Despite two decades of incremental approaches, inconsistency and inequity persist in the promotion process for clinician-educators. The authors propose five steps to mark a new approach to academic advancement for clinician-educators: (1) elevate the scholarly approach to teaching over peer-reviewed publications; (2) allow clinician-educators to identify an area of focus; (3) broaden the evidence for educational excellence; (4) prioritize internal referees; and (5) increase clinician-educator representation on promotion committees. Achieving meaningful change requires transforming entrenched traditions and policies at multiple levels. Changes that advance equity are necessary to retain academic faculty members who train the next generation of health professionals.

A Clinical Reasoning-Encoded Case Library Developed through Natural Language Processing.

IMPORTANCE: Case reports that externalize expert diagnostic reasoning are utilized for clinical reasoning instruction but are difficult to search based on symptoms, final diagnosis, or differential diagnosis construction. Computational approaches that uncover how experienced diagnosticians analyze the medical information in a case as they formulate a differential diagnosis can guide educational uses of case reports. OBJECTIVE: To develop a "reasoning-encoded" case database for advanced clinical reasoning instruction by applying natural language processing (NLP), a sub-field of artificial intelligence, to a large case report library. DESIGN: We collected 2525 cases from the New England Journal of Medicine (NEJM) Clinical Pathological Conference (CPC) from 1965 to 2020 and used NLP to analyze the medical terminology in each case to derive unbiased (not prespecified) categories of analysis used by the clinical discussant. We then analyzed and mapped the degree of category overlap between cases. RESULTS: Our NLP algorithms identified clinically relevant categories that reflected the relationships between medical terms (which included symptoms, signs, test results, pathophysiology, and diagnoses). NLP extracted 43,291 symptoms across 2525 cases and physician-annotated 6532 diagnoses (both primary and related diagnoses). Our unsupervised learning computational approach identified 12 categories of medical terms that characterized the differential diagnosis discussions within individual cases. We used these categories to derive a measure of differential diagnosis similarity between cases and developed a website ( universeofcpc.com ) to allow visualization and exploration of 55 years of NEJM CPC case series. CONCLUSIONS: Applying NLP to curated instances of diagnostic reasoning can provide insight into how expert clinicians correlate and coordinate disease categories and processes when creating a differential diagnosis. Our reasoning-encoded CPC case database can be used by clinician-educators to design a case-based curriculum and by physicians to direct their lifelong learning efforts.

How to Keep Training-After Residency Training.

Lifelong learning in medicine is an important skill and ethical obligation, but many residents do not feel prepared to be effective self-directed learners when training ends. The learning sciences offer evidence to guide self-directed learning, but these insights have not been integrated into a practical and actionable plan for residents to improve their clinical knowledge and reasoning. We encourage residents to establish a self-directed learning plan, just as an athlete employs a training plan in the pursuit of excellence. We highlight four evidence-based learning principles (spaced practice, mixed practice, retrieval practice, and feedback) and four training strategies comprising a weekly training plan: case tracking, simulated cases, quizzing, and new evidence integration. We provide tips for residents to implement and refine their approach and discuss how residency programs can foster these routines and habits. By optimizing their scarce self-directed learning time with a training plan, residents may enhance patient care and their career satisfaction through their pursuit of clinical mastery.

Patient Advocacy Assessment in the Medicine Clerkship: A Qualitative Study of Definition, Context, and Impact.

BACKGROUND: Advocacy is a core value of the medical profession. However, patient advocacy (advocacy) is not uniformly assessed and there are no studies of the behaviors clinical supervisors consider when assessing advocacy. OBJECTIVE: To explore how medical students and supervisors characterize advocacy during an internal medicine clerkship, how assessment of advocacy impacted students and supervisors, and elements that support effective implementation of advocacy assessment. DESIGN: A constructivist qualitative paradigm was used to understand advocacy assessment from the perspectives of students and supervisors. PARTICIPANTS: Medical students who completed the internal medicine clerkship at UCSF during the 2018 and 2019 academic years and supervisors who evaluated students during this period. APPROACH: Supervisor comments from an advocacy assessment item in the medicine clerkship and transcripts of focus groups were used to explore which behaviors students and supervisors deem to be advocacy. Separate focus groups with both students and supervisors examined the impact that advocacy assessment had on students' and supervisors' perceptions of advocacy and what additional context was necessary to effectively implement advocacy assessment. KEY RESULTS: Students and supervisors define advocacy as identifying and addressing social determinants of health, recognizing and addressing patient wishes and concerns, navigating the health care system, conducting appropriate evaluation and treatment, and creating exceptional therapeutic alliances. Effective implementation of advocacy assessment requires the creation of non-hierarchical team environments, supervisor role modeling, and pairing assessment with teaching of advocacy skills. Inclusion of advocacy assessment reflects and dictates institutional priorities, shapes professional identity formation, and enhances advocacy skill development for students and their supervisors. CONCLUSIONS: Students and supervisors consider advocacy to be a variety of behaviors beyond identifying and addressing social determinants of health. Effectively implementing advocacy assessment shapes students' professional identity formation, underscoring the critical importance of formally focusing on this competency in the health professions education.

The Future Comes Early for Medical Educators.

Many experts have foretold of a digital transformation in medical education. Yet, until recently, day-to-day practices for frontline clinician-educators, who cherish close physical and intellectual contact between the patient, learner, and teacher, have remained largely unchanged. The COVID-19 pandemic disrupted that model and is forcing teachers to pursue new ways to reach learners. We provide a roadmap for educators to start their transformation from an analog to a digital approach by harnessing existing tools including podcasts, social media, and videoconferencing. Teachers will need to enhance the same pedagogical and interpersonal practices that underpin effective in-person education while they learn new skills as they become curators, creators, and moderators in the digital space. This adaptation is essential, as many of the changes in medical education spurred by COVID-19 will likely far outlast the pandemic.

Psychometric validation of the reconstructed version of the assessment of reasoning tool.

BACKGROUND: Assessing learners' competence in diagnostic reasoning is challenging and unstandardized in medical education. We developed a theory-informed, behaviorally anchored rubric, the Assessment of Reasoning Tool (ART), with content and response process validity. This study gathered evidence to support the internal structure and the interpretation of measurements derived from this tool. METHODS: We derived a reconstructed version of ART (ART-R) as a 15-item, 5-point Likert scale using the ART domains and descriptors. A psychometric evaluation was performed. We created 18 video variations of learner oral presentations, portraying different performance levels of the ART-R. RESULTS: 152 faculty viewed two videos and rated the learner globally and then using the ART-R. The confirmatory factor analysis showed a favorable comparative fit index = 0.99, root mean square error of approximation = 0.097, and standardized root mean square residual = 0.026. The five domains, hypothesis-directed information gathering, problem representation, prioritized differential diagnosis, diagnostic evaluation, and awareness of cognitive tendencies/emotional factors, had high internal consistency. The total score for each domain had a positive association with the global assessment of diagnostic reasoning. CONCLUSIONS: Our findings provide validity evidence for the ART-R as an assessment tool with five theoretical domains, internal consistency, and association with global assessment.

Decisions in the Dark: An Educational Intervention to Promote Reflection and Feedback on Night Float Rotations.

BACKGROUND: Night float rotations, where residents admit patients to the hospital, are opportunities for practice-based learning. However, night float residents receive little feedback on their diagnostic and management reasoning, which limits learning. AIM: Improve night float residents' practice-based learning skills through feedback solicitation and chart review with guided reflection. SETTING/PARTICIPANTS: Second- and third-year internal medicine residents on a 1-month night float rotation between January and August 2017. PROGRAM DESCRIPTION: Residents performed chart review of a subset of patients they admitted during a night float rotation and completed reflection worksheets detailing patients' clinical courses. Residents solicited feedback regarding their initial management from day team attending physicians and senior residents. PROGRAM EVALUATION: Sixty-eight of 82 (83%) eligible residents participated in this intervention. We evaluated 248 reflection worksheets using content analysis. Major themes that emerged from chart review included residents' identification of future clinical practice changes, evolution of differential diagnoses, recognition of clinical reasoning gaps, and evaluation of resident-provider interactions. DISCUSSION: Structured reflection and feedback during night float rotations is an opportunity to improve practice-based learning through lessons on disease progression, clinical reasoning, and communication.